. _:b433597775 "2"^^ . _:b433597771 . _:b433597774 "2"^^ . _:b433597770 . . _:b7762630 "activating PDH, promotes mitochondrial respiration that leads to depolarisation of the intrinsic mitochondrial membrane, and induces apoptosis by the proximal mitochondrial pathway as described in the previous studies (Bonnet et al, >>2007<<; Cao et al, 2008; Wong et al, 2008). Induction of apoptosis and changes in mitochondrial function were most pronounced in the highly invasive and metastatic LoVo cells than the less invasive HT29 and SW480 cells." . _:b433597769 "2"^^ . _:b433597604 . _:b433597781 . _:b433597651 . . _:b433597768 "2"^^ . _:b433597724 . _:b433597780 . _:b433597771 "2"^^ . _:b433597783 . _:b433597770 "2"^^ . _:b433597782 . _:b433597781 "2"^^ . _:b433597777 . . _:b433597767 . _:b433597780 "2"^^ . _:b433597776 . _:b433597757 . _:b433597783 "2"^^ . _:b433597779 . _:b433597782 "2"^^ . _:b433597778 . . _:b433597813 . _:b433597777 "2"^^ . . _:b433597789 . . _:b433597776 "2"^^ . _:b433597629 . _:b433597788 . _:b433597617 . _:b433597779 "2"^^ . _:b433597725 . _:b7762623 "discussion" . _:b433597800 . _:b433597791 . _:b433597764 . _:b433597667 . _:b433597778 "2"^^ . _:b433597790 . . . _:b433597789 "2"^^ . _:b433597621 . _:b433597785 . _:b433597788 . _:b433597788 "2"^^ . . _:b433597784 . _:b433597620 . _:b433597791 "2"^^ . _:b433597787 . _:b433597638 . _:b433597790 "2"^^ . _:b433597786 . . _:b433597785 "2"^^ . _:b433597727 . _:b433597797 . _:b433597784 "2"^^ . _:b433597796 . _:b433597802 . _:b433597787 "2"^^ . _:b433597799 . . . . _:b433597786 "2"^^ . _:b433597798 . . . _:b433597797 "2"^^ . _:b433597793 . _:b7762627 "Intriguingly, Cao et al (>>2008<<) found that the combination of DCA and radiotherapy arrested prostate cancer cells in G2 phase, although DCA on its own did not affect cell-cycle profile." . _:b433597796 "2"^^ . . _:b433597792 . _:b433597628 . _:b433597642 . _:b7762623 . . _:b433597799 "2"^^ . _:b433597795 . . . _:b7762642 "It was suggested that DCA could rapidly translate to early-phase cancer clinical trials (Michelakis et al, >>2008<<). However, the dose of DCA required to inhibit growth of colorectal cancer cells in our study is unlikely to be achieved clinically without causing significant side effects. The dose of DCA required to achieve the equivalent plasma" . _:b433597798 "2"^^ . _:b433597794 . _:b433597741 . _:b433597793 "2"^^ . _:b433597805 . . _:b433597792 "2"^^ . _:b433597804 . . _:b433597831 . _:b433597819 . _:b433597795 "2"^^ . _:b433597807 . _:b433597684 . _:b433597794 "2"^^ . . _:b433597806 . . _:b433597644 . . _:b433597805 "2"^^ . . _:b433597801 . . _:b433597804 "2"^^ . _:b433597728 . _:b433597800 . _:b433597807 "2"^^ . "PMC0" . _:b433597803 . . _:b433597721 . _:b433597675 . _:b433597806 "2"^^ . _:b433597802 . . _:b433597814 . _:b433597801 "2"^^ . . _:b433597813 . _:b433597655 . _:b433597790 . _:b433597800 "2"^^ . . _:b433597812 . _:b433597803 "2"^^ . _:b433597815 . . _:b433597686 . _:b433597681 . . . _:b433597802 "2"^^ . _:b433597814 . . _:b433597607 . _:b433597813 "2"^^ . _:b433597809 . _:b433597627 . _:b433597812 "2"^^ . _:b433597650 . _:b433597808 . _:b433597815 "2"^^ . _:b433597811 . _:b433597814 "2"^^ . _:b7762647 . _:b433597810 . _:b433597809 "2"^^ . _:b433597821 . _:b433597773 . _:b433597605 . _:b433597808 "2"^^ . _:b433597789 . _:b433597820 . _:b433597623 . . . _:b433597604 . _:b433597811 "2"^^ . _:b433597739 . _:b433597823 . _:b433597607 . _:b433597810 "2"^^ . . _:b433597822 . _:b433597806 . _:b433597652 . _:b433597606 . _:b433597821 "2"^^ . . _:b433597817 . . _:b433597820 "2"^^ . _:b7762631 . _:b433597816 . _:b433597829 . _:b433597613 . _:b433597703 . _:b433597823 "2"^^ . . _:b433597819 . _:b433597674 . _:b433597603 . _:b433597822 "2"^^ . _:b433597818 . _:b433597602 . _:b433597817 "2"^^ . _:b433597829 . _:b433597613 . _:b7762627 . _:b433597816 "2"^^ . _:b433597730 . _:b433597759 . _:b433597828 . . _:b433597676 . _:b433597612 . _:b7762624 . _:b433597819 "2"^^ . _:b433597718 . _:b433597761 . _:b433597831 . _:b433597615 . _:b433597818 "2"^^ . _:b433597752 . _:b433597634 . _:b433597830 . _:b433597614 . _:b433597829 "2"^^ . _:b433597825 . . _:b433597609 . _:b433597828 "2"^^ . . . _:b433597824 . . _:b433597608 . _:b7762639 "100\u2009mg\u2009kg\u22121 DCA are on the nervous system and the liver, causing mild sedation or drowsiness, reversible peripheral neuropathy, and mild asymptomatic elevation of serum transaminases reflecting hepatocellular damage (Stacpoole et al, >>1998<<). In addition, recent studies reported that DCA effectively reduced tumour growth in clinically achievable doses both in vitro and in vivo (Bonnet et al, 2007; Sun et al, 2009)." . _:b433597831 "2"^^ . _:b433597737 . _:b433597827 . _:b433597766 . _:b433597782 . _:b433597611 . _:b433597830 "2"^^ . _:b433597826 . _:b433597756 . _:b433597665 . _:b433597610 . _:b433597825 "2"^^ . . _:b433597621 . _:b433597824 "2"^^ . _:b433597632 . _:b433597620 . _:b433597827 "2"^^ . _:b433597623 . _:b433597826 "2"^^ . _:b433597622 . _:b433597817 . _:b433597749 . _:b433597669 . _:b433597617 . . . _:b433597696 . _:b433597616 . . _:b433597753 . . _:b7762646 . _:b433597619 . _:b7762640 "In addition, recent studies reported that DCA effectively reduced tumour growth in clinically achievable doses both in vitro and in vivo (Bonnet et al, >>2007<<; Sun et al, 2009)." . _:b433597618 . _:b433597792 . . _:b433597656 . _:b433597629 . . _:b433597628 . . _:b433597631 . _:b433597633 . _:b433597630 . _:b433597625 . _:b433597777 . _:b433597726 . _:b433597624 . _:b433597693 . . _:b433597627 . _:b433597626 . . _:b433597637 . _:b433597637 . . . _:b433597636 . _:b433597615 . _:b433597639 . _:b433597638 . _:b7762646 "Dichloroacetate is a non-specific inhibitor of PDK (Whitehouse and Randle, >>1973<<), and has a different Ki for each of the four PDK isoenzymes (Bowker-Kinley et al, 1998)." . _:b433597633 . _:b433597679 . . _:b433597632 . . _:b433597635 . . _:b433597666 . _:b433597634 . _:b433597622 . _:b433597783 . _:b433597641 . _:b433597723 . _:b433597645 . _:b433597644 . _:b433597827 . _:b433597647 . . _:b433597646 . _:b433597641 . _:b433597769 . . _:b433597640 . _:b433597754 . . _:b433597701 . _:b433597643 . . _:b433597642 . _:b433597704 . _:b7762628 . _:b433597653 . _:b7762647 "Dichloroacetate is a non-specific inhibitor of PDK (Whitehouse and Randle, 1973), and has a different Ki for each of the four PDK isoenzymes (Bowker-Kinley et al, >>1998<<). In addition, the four PDK isoenzymes are known to be differentially expressed in various tissues. Thus, there is a need to develop inhibitors to the individual PDK isoenzymes that should allow cancer cell-type-specific metabolic" . _:b433597652 . . . . _:b433597655 . _:b7762625 . . _:b433597654 . . . . _:b433597649 . . . _:b433597643 . _:b433597746 . . . _:b433597648 . _:b433597712 . . . . _:b7762626 . _:b433597651 . _:b433597729 . . _:b433597650 . . . . _:b7762636 . _:b433597661 . . _:b433597660 . _:b433597690 . . . . _:b433597733 . _:b433597663 . _:b433597662 . . _:b7762632 . _:b433597657 . _:b433597656 . . . _:b433597663 . _:b7762634 . _:b433597639 . . _:b433597659 . . _:b7762645 . _:b433597658 . . _:b433597614 . _:b433597669 . _:b433597616 . _:b433597668 . . _:b433597671 . _:b433597762 . _:b433597786 . . _:b433597670 . _:b7762638 "Dichloroacetate has been found to be relatively safe in humans when used for treatment of lactic acidosis (Stacpoole et al, >>2003<<). The main side effects with up to 100\u2009mg\u2009kg\u22121 DCA are on the nervous system and the liver, causing mild sedation or drowsiness, reversible peripheral neuropathy, and mild asymptomatic elevation of serum transaminases reflecting" . . . . . _:b433597665 . _:b433597747 . _:b433597664 . _:b7762625 "This is in contrast to previous studies, which have shown G1 arrest or no change on cell-cycle profile with DCA treatment (Cao et al, 2008; Wong et al, >>2008<<). Wong et al (2008) showed increased expression of PUMA in all the endometrial cancer cell lines that had an apoptotic response to DCA, and concluded that this p53 activation led to G1 arrest. However, colorectal cancer cells in our study" . _:b433597683 . _:b433597667 . . _:b433597666 . . _:b433597677 . . _:b7762641 "In addition, recent studies reported that DCA effectively reduced tumour growth in clinically achievable doses both in vitro and in vivo (Bonnet et al, 2007; Sun et al, >>2009<<). It was suggested that DCA could rapidly translate to early-phase cancer clinical trials (Michelakis et al, 2008). However, the dose of DCA required to inhibit growth of colorectal cancer cells in our study is unlikely to be achieved" . . _:b433597676 . _:b433597807 . . _:b433597679 . . _:b433597678 . . _:b433597673 . . _:b433597636 . _:b433597672 . . . _:b433597675 . _:b433597822 . _:b433597732 . . _:b433597674 . _:b7762636 "This is in contrast to previous studies that have reported DCA to reduce proliferation and induce apoptosis in cancer cells with doses as low as 0.5\u201310\u2009mM (Bonnet et al, 2007; Wong et al, >>2008<<; Sun et al, 2009)." . . _:b433597810 . _:b7762644 "These results were markedly different to the effects of DCA observed on lung (Bonnet et al, >>2007<<), endometrial (Wong et al, 2008), and colorectal cancer cells in our study." . _:b433597685 . . . _:b433597684 . . . _:b433597687 . _:b433597607 "11"^^ . . _:b433597686 . _:b433597668 . _:b433597603 "23"^^ . _:b433597602 "28"^^ . _:b433597681 . _:b433597680 . . . _:b433597683 . . _:b7762639 . _:b433597682 . . _:b433597604 "20"^^ . _:b433597605 "17"^^ . _:b433597693 . _:b433597694 . _:b433597770 . _:b433597606 "17"^^ . _:b433597692 . _:b433597695 . _:b433597664 . _:b7762633 "In support of this, a recent study reported that the colorectal tumours resistant to 5-fluorouracil are more likely to have upregulated glycolysis, and hence more amenable to therapy targeting cancer metabolism (Shin et al, >>2009<<). In this regard, our results contrast the findings of Wong et al (2008), who found highly invasive endometrial cancer cells to be most resistant to DCA treatment." . _:b433597614 "7"^^ . _:b433597694 . _:b433597615 "7"^^ . _:b433597671 . _:b433597689 . . _:b433597787 . _:b433597612 "8"^^ . . . _:b433597688 . _:b433597613 "7"^^ . _:b433597691 . _:b433597830 . . . _:b433597653 . _:b433597610 "9"^^ . _:b433597690 . _:b433597611 "8"^^ . _:b433597784 . . . _:b433597628 . _:b433597734 . _:b433597692 . _:b433597629 . _:b433597699 . . _:b433597608 "10"^^ . _:b433597760 . _:b433597630 . _:b433597631 . _:b433597624 . _:b433597804 . _:b433597609 "9"^^ . _:b433597625 . _:b433597622 "6"^^ . _:b433597626 . _:b433597627 . _:b433597620 . _:b433597621 . _:b433597623 "6"^^ . _:b433597622 . _:b433597623 . "10.1038%2Fsj.bjc.6605701" . . _:b433597616 . . _:b433597617 . . _:b433597618 . _:b433597620 "6"^^ . _:b433597619 . _:b433597612 . _:b433597613 . _:b433597621 "6"^^ . _:b433597614 . _:b433597615 . . _:b433597608 . _:b433597609 . _:b433597618 "6"^^ . _:b433597610 . _:b433597662 . _:b433597611 . _:b433597604 . _:b433597799 . _:b433597605 . _:b433597619 "6"^^ . _:b433597606 . _:b433597607 . _:b7762634 "In this regard, our results contrast the findings of Wong et al (>>2008<<), who found highly invasive endometrial cancer cells to be most resistant to DCA treatment." . _:b433597670 . _:b433597616 "6"^^ . _:b433597602 . _:b433597603 . . _:b433597660 . . _:b7762644 . _:b433597661 . _:b433597654 . _:b433597617 "6"^^ . _:b433597662 . _:b433597663 . _:b433597656 . _:b433597797 . . _:b433597697 . _:b433597657 . _:b433597658 . _:b433597659 . _:b433597652 . _:b433597629 "5"^^ . _:b433597605 . _:b433597653 . _:b433597654 . _:b433597771 . _:b433597655 . _:b433597648 . _:b433597628 "5"^^ . _:b433597649 . _:b433597650 . _:b433597651 . _:b433597644 . _:b433597631 "5"^^ . _:b7762640 . _:b433597645 . _:b433597646 . _:b433597647 . _:b433597624 . _:b433597640 . _:b433597630 "5"^^ . _:b433597641 . _:b433597642 . _:b433597643 . _:b433597805 . _:b433597742 . _:b433597708 . _:b433597636 . _:b433597625 "5"^^ . _:b433597637 . . _:b433597638 . _:b433597639 . _:b433597791 . _:b433597632 . _:b433597624 "5"^^ . _:b433597633 . _:b433597634 . _:b433597635 . _:b433597692 . _:b433597627 "5"^^ . _:b433597722 . _:b433597693 . _:b433597694 . _:b433597695 . _:b433597688 . _:b433597626 "5"^^ . _:b433597689 . _:b433597690 . _:b433597691 . _:b433597637 "4"^^ . _:b433597684 . . . _:b433597685 . _:b433597686 . _:b433597687 . _:b433597636 "4"^^ . _:b433597680 . _:b433597681 . _:b433597682 . _:b433597683 . _:b433597639 "4"^^ . _:b433597676 . . _:b433597677 . _:b433597678 . _:b433597679 . _:b433597638 "4"^^ . _:b433597672 . _:b433597626 . _:b433597673 . . . _:b433597674 . _:b433597648 . _:b433597675 . _:b433597668 . _:b433597633 "5"^^ . _:b7762630 . _:b433597669 . . _:b433597670 . _:b433597671 . _:b433597702 . . _:b433597664 . . _:b433597632 "5"^^ . _:b433597665 . _:b433597666 . _:b7762629 . . _:b433597667 . _:b7762642 . _:b433597635 "5"^^ . . . _:b433597634 "5"^^ . _:b433597645 "4"^^ . _:b433597644 "4"^^ . _:b433597677 . _:b433597647 "4"^^ . . _:b433597646 "4"^^ . _:b433597640 . _:b433597641 "4"^^ . _:b433597640 "4"^^ . _:b433597818 . _:b433597735 . _:b433597685 . _:b433597643 "4"^^ . _:b433597680 . . _:b433597642 "4"^^ . _:b7762635 . . _:b433597768 . _:b433597653 "3"^^ . . _:b433597794 . _:b433597709 . . _:b433597652 "3"^^ . . . _:b433597608 . _:b433597655 "3"^^ . _:b433597682 . _:b7762628 "A similar finding was reported by Wong et al (>>2008<<) in one of several endometrial cancer cells tested." . _:b433597713 . _:b433597654 "3"^^ . . . _:b433597649 "4"^^ . _:b433597743 . _:b433597815 . _:b433597648 "4"^^ . _:b433597651 "3"^^ . . _:b433597650 "3"^^ . . . _:b433597661 "3"^^ . _:b433597660 "3"^^ . _:b433597809 . _:b433597663 "3"^^ . _:b433597710 . _:b7762623 . _:b433597816 . _:b433597662 "3"^^ . . . _:b433597705 . _:b433597657 "3"^^ . . _:b433597656 "3"^^ . _:b433597688 . _:b433597796 . _:b433597659 "3"^^ . _:b433597658 "3"^^ . _:b433597646 . _:b7762628 . . _:b433597669 "3"^^ . _:b7762629 . _:b433597668 "3"^^ . _:b7762630 . _:b433597649 . _:b433597671 "3"^^ . . _:b7762631 . _:b433597823 . _:b433597779 . . . _:b433597670 "3"^^ . _:b7762624 . _:b433597611 . . _:b433597665 "3"^^ . _:b433597781 . _:b7762625 . _:b433597689 . _:b433597664 "3"^^ . _:b433597630 . . . _:b7762626 . . . _:b433597667 "3"^^ . _:b7762627 . . _:b433597645 . _:b433597666 "3"^^ . . _:b7762636 . _:b433597603 . _:b433597677 "3"^^ . _:b7762637 . _:b433597676 "3"^^ . _:b7762638 . _:b433597679 "3"^^ . _:b7762639 . _:b7762638 . _:b433597678 "3"^^ . _:b433597631 . _:b7762632 . . _:b433597720 . _:b433597673 "3"^^ . _:b433597828 . _:b7762633 . _:b433597829 . _:b433597657 . . _:b433597830 . _:b433597831 . _:b433597672 "3"^^ . _:b433597824 . _:b7762635 "This is in contrast to previous studies that have reported DCA to reduce proliferation and induce apoptosis in cancer cells with doses as low as 0.5\u201310\u2009mM (Bonnet et al, >>2007<<; Wong et al, 2008; Sun et al, 2009)." . _:b7762634 . _:b433597803 . _:b433597825 . _:b433597826 . _:b433597827 . _:b433597675 "3"^^ . _:b7762635 . . _:b433597674 "3"^^ . _:b7762637 "This is in contrast to previous studies that have reported DCA to reduce proliferation and induce apoptosis in cancer cells with doses as low as 0.5\u201310\u2009mM (Bonnet et al, 2007; Wong et al, 2008; Sun et al, >>2009<<). Dichloroacetate has been found to be relatively safe in humans when used for treatment of lactic acidosis (Stacpoole et al, 2003). The main side effects with up to 100\u2009mg\u2009kg\u22121 DCA are on the nervous system and the liver, causing mild" . _:b7762644 . . _:b433597685 "3"^^ . _:b7762645 . . _:b433597684 "3"^^ . . _:b7762646 . _:b433597706 . . _:b433597717 . _:b433597695 . _:b433597687 "2"^^ . _:b433597826 . _:b7762647 . _:b433597686 "2"^^ . _:b7762640 . _:b433597736 . . _:b433597678 . _:b433597681 "3"^^ . _:b7762641 . . _:b433597680 "3"^^ . _:b7762642 . . . _:b433597683 "3"^^ . _:b7762643 . _:b433597635 . _:b433597682 "3"^^ . . _:b433597776 . _:b433597693 "2"^^ . _:b433597610 . _:b433597692 "2"^^ . . . _:b433597695 "2"^^ . . . _:b433597694 "2"^^ . _:b433597689 "2"^^ . _:b433597687 . _:b433597701 . . _:b433597688 "2"^^ . _:b433597700 . _:b433597625 . _:b433597691 "2"^^ . _:b433597673 . _:b433597748 . _:b433597703 . . . . _:b433597690 "2"^^ . _:b433597702 . _:b433597701 "2"^^ . _:b433597697 . _:b433597774 . . _:b433597700 "2"^^ . . _:b433597696 . _:b433597703 "2"^^ . _:b433597699 . _:b7762633 . _:b433597702 "2"^^ . _:b433597698 . _:b433597697 "2"^^ . _:b433597709 . _:b433597740 . . . _:b433597696 "2"^^ . _:b433597708 . _:b433597772 . _:b433597699 "2"^^ . _:b433597711 . _:b433597724 . _:b433597778 . _:b433597725 . _:b433597726 . _:b433597698 "2"^^ . _:b433597727 . _:b433597710 . _:b433597720 . _:b433597721 . . _:b433597709 "2"^^ . _:b433597722 . _:b433597723 . _:b433597758 . _:b433597705 . _:b433597716 . . _:b433597717 . _:b433597718 . _:b433597708 "2"^^ . . _:b433597719 . _:b433597704 . _:b433597712 . _:b433597713 . _:b433597714 . _:b433597711 "2"^^ . . _:b433597658 . _:b433597707 . _:b433597715 . _:b433597708 . _:b433597785 . _:b433597709 . _:b433597821 . . _:b433597710 . _:b433597710 "2"^^ . _:b433597711 . _:b433597820 . _:b433597707 . _:b433597706 . _:b433597704 . _:b433597660 . _:b433597705 . _:b433597706 . _:b433597705 "2"^^ . _:b433597707 . _:b433597717 . . _:b433597700 . . _:b433597701 . _:b433597702 . _:b433597828 . _:b433597704 "2"^^ . _:b433597703 . _:b433597716 . _:b433597696 . _:b433597697 . _:b433597698 . _:b433597707 "2"^^ . _:b433597699 . _:b433597719 . _:b433597756 . _:b433597757 . _:b433597758 . _:b433597706 "2"^^ . _:b433597759 . _:b7762629 "a proportion of the cells observed to be in \u2018S phase\u2019 after DCA treatment of the cancer cell lines actually represent apoptotic cells in the \u2018sub-G2\u2019 region, as has been reported previously in lymphoma cells (Klucar and Al-Rubeai, >>1997<<)." . _:b433597718 . _:b433597752 . _:b433597753 . _:b433597754 . _:b433597717 "2"^^ . _:b433597755 . _:b433597795 . _:b433597713 . . _:b433597748 . _:b433597749 . _:b433597750 . _:b433597716 "2"^^ . _:b433597751 . _:b433597712 . _:b433597744 . _:b433597745 . . _:b433597746 . _:b433597719 "2"^^ . _:b433597747 . _:b433597715 . _:b433597740 . _:b433597741 . _:b433597742 . _:b433597718 "2"^^ . _:b433597743 . _:b433597714 . _:b433597736 . _:b433597737 . _:b433597738 . _:b433597713 "2"^^ . _:b433597739 . _:b7762645 "These results were markedly different to the effects of DCA observed on lung (Bonnet et al, 2007), endometrial (Wong et al, >>2008<<), and colorectal cancer cells in our study." . _:b433597725 . _:b433597732 . _:b433597733 . _:b433597734 . _:b433597798 . _:b433597712 "2"^^ . _:b433597735 . _:b433597724 . _:b433597728 . _:b433597729 . _:b433597730 . _:b433597715 "2"^^ . _:b433597731 . _:b433597727 . _:b433597788 . _:b433597789 . _:b433597790 . _:b433597714 "2"^^ . _:b433597791 . _:b433597726 . _:b7762623 _:b7762640 . _:b433597784 . _:b7762623 _:b7762641 . _:b433597785 . _:b7762623 _:b7762642 . _:b433597786 . _:b433597725 "2"^^ . _:b7762623 _:b7762643 . _:b433597787 . _:b433597721 . _:b7762623 _:b7762644 . _:b433597780 . _:b7762623 _:b7762645 . _:b433597647 . _:b7762623 _:b7762646 . _:b433597781 . . _:b433597755 . _:b433597724 "2"^^ . _:b7762623 _:b7762647 . _:b433597782 . _:b433597783 . _:b433597720 . _:b7762623 _:b7762632 . _:b433597776 . _:b7762623 _:b7762633 . _:b433597777 . _:b7762623 _:b7762634 . . _:b433597727 "2"^^ . _:b7762623 _:b7762635 . _:b433597778 . _:b433597779 . _:b433597723 . _:b433597609 . _:b7762623 _:b7762636 . _:b433597772 . _:b7762623 _:b7762637 . _:b433597773 . _:b7762637 . _:b7762623 _:b7762638 . _:b433597774 . _:b433597726 "2"^^ . _:b7762623 _:b7762639 . _:b433597775 . _:b433597722 . _:b7762623 _:b7762624 . _:b433597768 . _:b433597801 . _:b7762623 _:b7762625 . _:b433597769 . _:b7762623 _:b7762626 . _:b433597770 . _:b433597721 "2"^^ . _:b7762623 _:b7762627 . _:b433597771 . _:b433597733 . . _:b7762623 _:b7762628 . _:b433597764 . _:b7762623 _:b7762629 . _:b433597765 . _:b7762623 _:b7762630 . _:b433597766 . _:b433597720 "2"^^ . . _:b7762623 _:b7762631 . _:b433597767 . _:b433597732 . _:b433597760 . _:b433597761 . _:b433597762 . _:b433597723 "2"^^ . . _:b433597735 . _:b433597763 . _:b433597820 . _:b433597821 . _:b7762626 "Wong et al (>>2008<<) showed increased expression of PUMA in all the endometrial cancer cell lines that had an apoptotic response to DCA, and concluded that this p53 activation led to G1 arrest." . _:b433597822 . _:b433597722 "2"^^ . _:b433597823 . _:b433597734 . _:b433597816 . _:b433597817 . _:b433597659 . _:b433597818 . _:b433597733 "2"^^ . . . . _:b433597819 . _:b433597729 . _:b433597812 . _:b433597813 . _:b433597716 . _:b433597814 . _:b433597732 "2"^^ . _:b433597815 . _:b433597728 . _:b433597808 . . _:b433597745 . _:b433597809 . _:b433597810 . _:b433597744 . _:b433597735 "2"^^ . _:b433597811 . _:b433597731 . . _:b433597804 . _:b433597805 . _:b433597602 . _:b433597734 "2"^^ . _:b433597806 . _:b433597807 . _:b433597730 . _:b433597800 . _:b433597801 . . _:b433597825 . _:b433597729 "2"^^ . _:b433597802 . _:b433597803 . _:b433597741 . _:b433597796 . . _:b433597797 . _:b433597798 . _:b433597728 "2"^^ . . _:b433597740 . _:b433597799 . _:b433597792 . _:b433597751 . _:b433597793 . _:b433597794 . _:b433597731 "2"^^ . _:b433597795 . _:b433597743 . _:b433597714 . _:b433597730 "2"^^ . . _:b433597742 . _:b433597741 "2"^^ . _:b433597737 . _:b433597775 . _:b433597740 "2"^^ . _:b433597736 . _:b433597824 . _:b7762632 "respiration that leads to depolarisation of the intrinsic mitochondrial membrane, and induces apoptosis by the proximal mitochondrial pathway as described in the previous studies (Bonnet et al, 2007; Cao et al, 2008; Wong et al, >>2008<<). Induction of apoptosis and changes in mitochondrial function were most pronounced in the highly invasive and metastatic LoVo cells than the less invasive HT29 and SW480 cells." . . _:b433597743 "2"^^ . _:b433597739 . _:b433597742 "2"^^ . _:b433597738 . . _:b433597780 . . _:b433597737 "2"^^ . . _:b433597749 . . _:b7762643 . _:b433597736 "2"^^ . _:b433597700 . _:b433597748 . _:b433597750 . . _:b433597812 . _:b433597739 "2"^^ . _:b433597751 . _:b433597618 . _:b433597619 . _:b7762641 . _:b433597738 "2"^^ . _:b433597750 . _:b433597749 "2"^^ . _:b433597745 . _:b433597661 . _:b433597748 "2"^^ . _:b433597744 . _:b433597751 "2"^^ . . _:b433597747 . . _:b433597691 . _:b433597750 "2"^^ . _:b433597746 . . _:b433597745 "2"^^ . _:b433597757 . _:b433597744 "2"^^ . _:b433597756 . . _:b433597747 "2"^^ . _:b433597606 . _:b433597759 . . _:b433597746 "2"^^ . _:b433597758 . _:b7762643 "Intriguingly, Sun et al (>>2009<<) in their study on breast cancer cells found that DCA inhibited proliferation of cancer cells, but did not induce apoptosis or cell death." . . _:b7762631 "promotes mitochondrial respiration that leads to depolarisation of the intrinsic mitochondrial membrane, and induces apoptosis by the proximal mitochondrial pathway as described in the previous studies (Bonnet et al, 2007; Cao et al, >>2008<<; Wong et al, 2008). Induction of apoptosis and changes in mitochondrial function were most pronounced in the highly invasive and metastatic LoVo cells than the less invasive HT29 and SW480 cells." . _:b433597757 "2"^^ . . _:b433597753 . . _:b433597756 "2"^^ . _:b433597752 . _:b433597763 . _:b433597759 "2"^^ . _:b433597765 . _:b433597755 . . _:b433597811 . _:b433597758 "2"^^ . . _:b433597754 . . _:b433597753 "2"^^ . _:b433597765 . _:b433597793 . _:b433597752 "2"^^ . _:b433597764 . . . _:b433597755 "2"^^ . . _:b7762624 "This is in contrast to previous studies, which have shown G1 arrest or no change on cell-cycle profile with DCA treatment (Cao et al, >>2008<<; Wong et al, 2008)." . _:b433597767 . _:b433597754 "2"^^ . _:b433597766 . _:b433597765 "2"^^ . _:b433597761 . . _:b433597764 "2"^^ . _:b433597760 . _:b433597698 . _:b433597767 "2"^^ . . _:b433597763 . . _:b433597766 "2"^^ . _:b433597762 . . _:b433597731 . _:b433597761 "2"^^ . _:b433597773 . . _:b433597760 "2"^^ . _:b433597715 . _:b433597772 . _:b433597719 . _:b433597763 "2"^^ . _:b433597775 . _:b433597762 "2"^^ . _:b433597612 . _:b433597774 . . . _:b433597773 "2"^^ . _:b433597672 . _:b433597769 . _:b433597711 . . _:b433597772 "2"^^ . _:b433597738 . _:b433597768 . _:b433597808 .